Exposure to Aroclor 1254 persistently suppresses the functions of pancreatic β-cells and deteriorates glucose homeostasis in male mice

Environ Pollut. 2019 Jun;249:822-830. doi: 10.1016/j.envpol.2019.03.101. Epub 2019 Mar 27.

Abstract

Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants that have been shown to be related to the occurrence of type 2 diabetes mellitus (T2DM). Nevertheless, it is necessary to further explore the development of T2DM caused by PCBs and its underlying mechanisms. In the present study, 21-day-old C57BL/6 male mice were orally treated with Aroclor 1254 (0.5, 5, 50 or 500 μg kg-1) once every three days. After exposure for 66 d, the mice showed impaired glucose tolerance, 13% and 14% increased fasting serum insulin levels (FSIL), and 63% and 69% increases of the pancreatic β-cell mass in the 50 and 500 μg kg-1 groups, respectively. After stopping exposure for 90 d, treated mice returned to normoglycemia and normal FSIL. After re-exposure of these recovered mice to Aroclor 1254 for 30 d, fasting plasma glucose showed 15%, 28% and 16% increase in the 5, 50 and 500 μg kg-1 treatments, FSIL exhibited 35%, 27%, 30% and 32% decrease in the 0.5, 5, 50 or 500 μg kg-1 groups respectively, and there was no change in pancreatic β-cell mass. Transcription of the pancreatic insulin gene (Ins2) was significantly down-regulated in the 50 and 500 μg kg-1 groups, while DNA-methylation levels were simultaneously increased in the Ins2 promoter during the course of exposure, recovery and re-exposure. Reduced insulin levels were initially rescued by a compensative increase in β-cell mass. However, β-cell mass eventually failed to make sufficient levels of insulin, resulting in significant increases in fasting blood glucose, and indicating the development of T2DM.

Keywords: Dynamic effects; Epigenetic; Glucose homeostasis; Insulin level; Polychlorinated biphenyls.

MeSH terms

  • Animals
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Chlorodiphenyl (54% Chlorine) / administration & dosage
  • Chlorodiphenyl (54% Chlorine) / toxicity*
  • DNA Methylation / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology
  • Environmental Pollutants / administration & dosage
  • Environmental Pollutants / toxicity*
  • Homeostasis / drug effects*
  • Insulin / blood
  • Insulin / genetics
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / pathology
  • Male
  • Mice, Inbred C57BL

Substances

  • Blood Glucose
  • Environmental Pollutants
  • Ins2 protein, mouse
  • Insulin
  • Chlorodiphenyl (54% Chlorine)